Central blood pressure (BP) is physiologically and clinically more relevant than peripheral BP, especially in aging. However, peripheral BP waveforms can be measured more safely via catheterization and even non-invasively. The broad objective of this project is to establish a technique for mathematically deriving a central BP waveform from a peripheral BP waveform. While such techniques have been developed in the past, they are based on the assumption that a single, universal transfer function exists that can faithfully relate a peripheral BP waveform to a central BP waveform of any subject over any physiologic condition. These generalized transfer functions (GTF) techniques therefore do not adapt to the inter-subject and temporal variability of the arterial tree due to, for example, age-related arterial compliance differences and neuro-humoral modulation of peripheral resistance and are consequently prone to serious central BP error. In this project, a new technique, which is able to adapt the transfer function relating peripheral BP to central BP to the arterial parameters of the subject at the time of measurement by exploiting the fact that ascending aortic blood flow is negligible during diastole, will be rigorously investigated in humans as a follow-up to successful animal testing. The specific aims are: (1) to optimize the adaptive transfer function (ATF) technique for application in humans; (2) to broadly validate the technique in humans; and (3) to demonstrate that the technique is superior to previous techniques in humans. To accomplish these specific aims, existing data comprising non-invasive peripheral BP waveforms for analysis and reference central BP waveforms from a large number of diverse subjects under multiple physiologic conditions will be analyzed. A portion of the data will be used to maximize the accuracy of the ATF technique and enhance it in other ways including augmenting its computational speed. These data will likewise be used to optimize GTF techniques and other previous, related techniques. The remaining data will be used to evaluate the techniques in terms of accuracy and clinical value of the derived central BP as well as robustness to actual noise in the analyzed peripheral BP waveforms. Statistical comparisons will then be performed to establish the relative capabilities and any limitations of the ATF technique. Successful completion of this project will be followed by prospective patient testing of the ATF technique and may ultimately lead to improved BP monitoring in clinical practice.